Human Pluripotent Stem Cell Fate Regulation by SMARCB1

Ilana Carmel-Gross, Etgar Levy, Leah Armon, Orly Yaron, Hiba Waldman Ben-Asher, Achia Urbach

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Epigenetic regulation by the SWI/SNF complex is essential for normal self-renewal capacity and pluripotency of human pluripotent stem cells (hPSCs). It has been shown that different subunits of the complex have a distinct role in this regulation. Specifically, the SMARCB1 subunit has been shown to regulate the activity of enhancers in diverse types of cells, including hPSCs. Here, we report the establishment of conditional hPSC lines, enabling control of SMARCB1 expression from complete loss of function to significant overexpression. Using this system, we show that any deviation from normal SMARCB1 expression leads to cell differentiation. We further found that SMARCB1 expression is not required for differentiation of hPSCs into progenitor cells, but rather for later stages of differentiation. Finally, we identify SMARCB1 as a critical player in regulation of cell-cell and cell-ECM interactions in hPSCs and show that this regulation is mediated at least in part by the WNT pathway.

Original languageEnglish
Pages (from-to)1037-1046
Number of pages10
JournalStem Cell Reports
Volume15
Issue number5
DOIs
StatePublished - 10 Nov 2020

Bibliographical note

Publisher Copyright:
© 2020 The Authors

Funding

The authors thank Dr. Su-Chun Zhang (University of Wisconsin, Madison, WI, USA) for kindly providing the AAVS1-TRE3G-EGFP donor plasmid. This work was funded in part by the Israel Cancer Association (ICA), grant no. 20181072 .

FundersFunder number
Israel Cancer Association20181072

    Keywords

    • SMARCB1
    • SWI/SNF complex
    • extra cellular matrix
    • pluripotent stem cell

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